Gene mapping studies using DNA markers to detect craniofacial and oral diseases utilize a wide variety of statistical techniques. We are developing a scheme to better integrate these software tools. Since many of these programs were written elsewhere using a variety of computer languages and input formats, integrating them with our internal database will streamline the analysis process. We are constantly updating our suite of statistical analysis tools as the field of genetic epidemiology is under very rapid development, with improved methods and computer programs regularly being made available. For example, we developed and evaluated a new method to test for genotype by environment interactions for birth defects, where we look at not only the developing child's genotype but also that of the mother. Since the mother's body serves as a buffer or modulator of the developing child's environment, including its exposure to teratogenic substances such as cigarette smoke or alcohol, it seems especially important that the mother's genotype also be evaluated. In our studies of oral clefting, we have already found evidence of such maternal genotype effects for SNPs relevant to processing of these teratogens. In addition, we are continuing our efforts to improve the speed, accuracy and efficiency of genotyping for large-scale gene mapping studies. During the past year we have evaluated several alternative molecular marker sets for screening the entire human genome, including a newly available set of microsatellite markers based primarily on dinucleotide versus tetranucleotide repeats. Recent efforts have been focused on incorporating our new instruments into these analyses including DNA sequencers and a robotic laboratory workstation. In order to efficiently keep track of the very large amounts of information essential for conducting large-scale genetic epidemiological studies, we are continuously undertaking ongoing development of our comprehensive data management system. This system is used for the management of clinical, pedigree and genotype data for gene mapping studies and other study designs involving research aimed at the oral and dental disorders under investigation by the Senior Investigator. Our goal is to have a fully integrated system that can manage clinical information, family histories, and marker-allele typing. In addition, this system should provide interactive procedures including: (1) extensive error checking; (2) generation of formatted files suitable for input to various linkage analysis programs; and (3) provide primer inventories and for tracking DNA samples and other biological specimens and laboratory reagents.